Polymorphisms in CD31/PECAM-1 and CD38 Genes Are Associated with Susceptibility to Multiple Myeloma

Abstract

Interactions with bone marrow microenvironment play a major role in the control of multiple myeloma (MM) growth and survival. MM clonal plasma cells co-express high levels of a signaling receptor CD38 and its ligand, the platelet endothelial adhesion molecule-1, CD31//PECAM-1. Homotypic and heterotypic interactions through these adhesion molecules (CD31/CD31, CD38/CD31 and CD38/hyaluronate interactions) may be involved in the pathogenesis of MM. The objective of this study was to investigate whether inherited variants in CD31/PECAM-1 and CD38 genes influence on susceptibility to MM. A total of 189 Caucasian patients with MM and 209 healthy controls were genotyped with the use of PCR-based methods. Genotyping was performed to assess allelic frequencies of three non-synonymous single nucleotide polymorphisms (SNPs) in CD31/PECAM1 gene including 373C>G (Leu 125Val), 1688G>A (Ser563Asn) and 2008A>G (Arg670Gly) as well as two SNPs in CD38 gene including 184C>G in intron 1 and non-synonymous 418C>T (Arg140Trp) in exon 3. Analyzing the prevalence of investigated genetic variants, we found that allelic frequencies of two SNPs in CD31/PECAM-1 gene and intron 1 184C>G SNP in CD38 gene differed significantly between MM patients and controls. Concerning CD31/PECAM-1 SNPs, the carriership of 373G allele was associated with the relative risk of MM of 4.5 (p=8×10−10), while in carriers of 1688A allele the relative risk of MM reached 3.0 (p=2×10−6). Regarding CD38 gene, compared to wild-type 184C-allele carriers, the carriers of variant 184G-allele had 3.4-fold increased risk of MM (p=1×1−9). In conclusion, the results of this study suggest that inherited variants in ligand-receptor CD31/PECAM1 - CD38 system contribute to the genetic susceptibility to MM in Caucasians.